2,3,7,8-Tetrachlorodibenzo-p-dioxin inhibition of 17 beta-estradiol-induced increases in rat uterine epidermal growth factor receptor binding activity and gene expression.
Treatment of immature female Sprague-Dawley rats with 17 beta-estradiol (5 micrograms/animal) resulted in an increase in uterine epidermal growth factor (EGF) receptor binding activity. Moreover, in a separate study it was also shown that 17 beta-estradiol increased steady-state levels of rat uterine EGF receptor mRNA as determined by Northern analysis. In contrast, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) caused a dose-response decrease in constitutive rat uterine EGF receptor binding activity and this was paralleled by a decrease in steady-state levels of uterine EGF receptor mRNA. Cotreatment of the animals with both TCDD (16 nmol/kg) and 17 beta-estradiol (5 micrograms/rat) gave results which showed that TCDD significantly inhibited the estrogen-induced increases in rat uterine EGF receptor binding activity and EGF receptor mRNA levels. These results further extend the range of antiestrogenic properties of TCDD and suggest that the inhibition of growth factor expression may play a role in the growth-inhibiting properties of TCDD in estrogen-responsive tissues or cells.
Astroff
B
B
Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station 77843.
Rowlands
C
C
Dickerson
R
R
Safe
S
S
D000818:Animals; D003864:Depression, Chemical; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000096:biosynthesis; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism
D004965:Estrogen Antagonists; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D004958:Estradiol; D004815:Epidermal Growth Factor; D066246:ErbB Receptors